Abstract

Obesity is a disease that has reached epidemic proportions across the world. Many types of treatments have been used to combat obesity including using synthetic drugs such as sibutramine and orlistat. However, the high cost and potentially hazardous side-effects of anti-obesity drugs have led many researchers to turn to naturally occurring compounds obtained from fruits, vegetables, herbs and plants for the treatment of obesity. In our study, the anti-obesity effects of S. crispus crude extract (SCE) and individual polyphenols (EGCG, Resveratrol, Phloridzin, Quercetin and Verbascoside) found in fruits, vegetables and herbs have been investigated.

The effects of S. crispus extract (SCE) in vivo were tested on high fat-induced obese LDLr KO mice maintained on high fat diet (HFD) or switched to low fat diet (LFD). All mice were HFD for 25 weeks to induce obesity, after which half were maintained on the HFD and half switched to LFD. At the same time, mice were given normal water or 0.1% (w/v) SCE in water at Week 0-4 which was increased to 1% (w/v) at Week 5-10. Oxygen consumption (VO2), CO2 production (VCO2), RER, locomotor activity (LMA) and heat production (HP) were measured at Week 0, 5 and 10. Food intake, water intake and body weight was measured weekly. Plasma glycerol (PG) and abdominal adipose tissue (AAT) weight were determined at Week 10. Mice switched to LFD lost weight (p< 0.001), mainly due to decreased energy intake (p<0.001). They also had lower AAT weight and PG concentration (all p<0.001). SCE had no effect at either dose on body weight, VO2, VCO2 or LMA, but significantly reduced respiratory exchange ratio (RER) (p=0.034) and increased HP at Week 4 (P=0.048), without altering food or water intake (p=0.1, p=0.222). PG concentration were also increased in SCE treated mice (p=0.032).

The effects of SCE and individual polyphenols in vitro were tested on rat epididymal and human omental adipose tissue explants and results were compared with with the results from the pig perirenal adipose tissue explants. SCE does not appear to have any direct effect on lipolysis in the rat epididymal adipose tissue explants and human omental adipose tissue explants. EGCG was found to consistently inhibit lipolysis in rat, human and pig adipose tissue explants and the effects were greatest at 100µM. The effects of Phloridzin in human, rat and pig fat explants were inconsistent as it was found to either increase or decrease lipolysis with different treatments. In all experiments, when Isoproterenol (IP) was present Resveratrol inhibited lipolysis and was independent of adenosine deaminase (ADA), with greater inhibition found at 100µM compared with 50µM Resveratrol. The effects of Resveratrol on lipolysis in the human adipose tissue explants was found to be different when compared with the effects found in the pig and rat adipose tissue explants when incubated for 24 and 26hr. The effects of Resveratrol on lipolysis in the human adipose tissue itself are also dependent on the presence and absence of ADA and IP.

Subsequent experiments were carried out where basal lipolysis and effects of the presence and absence of ADA were also investigated. Basal lipolysis was found to be higher in pig adipose tissue explants (Headland, 2007) than in human adipose tissue explants, but lower than rat adipose tissue explants. This is also true for the IP stimulated lipolysis in pig perirenal adipose tissue explants, but not in the pig subcutaneous adipose tissue explants, where IP stimulated lipolysis was similar to that in human omental adipose tissue. As expected, the presence of adenosine does have an effect on the lipolysis rate in rat, human and pig adipose tissue explants, since the addition of ADA (to metabolise/remove adenosine) increased basal lipolysis. However, only in the pig perirenal adipose tissue explants was IP stimulated lipolysis found to be increased with ADA. In the human omental adipose tissue explants, we also found that although BMI and age had weak negative correlations with lipolysis, these were not statistically significant (P=0.097 for BMI, P=0.48 for age). However, the trend suggests that IP stimulated lipolysis decreased with increased BMI.

Thus, SCE appeared to induce lipolysis and body fat oxidation in vivo but no direct effect on lipolysis were found in vitro. Resveratrol is the most promising polyphenol to induce lipolysis based on the studies across the rat, human and pig species compared with quercetin, EGCG and Phloridzin. The consistent effects of EGCG on lipolysis inhibition however, might also be an anti-obesity effect through the mechanism of adipocyte apoptosis which requires further study.